The involved studies are aimed at defining the host responses crucial for defense against infection with Cryptococcus neoformans. At least half the cases of cryptococcosis occur in patients with impaired cell-mediated immunity. The mechanism of pathogenicity of C. neoformans is being investigated by critical examination of chemotaxis and phagocytosis by both granulocytes and macrophages of various isolates of C. neoformans differing in virulence. Lymphocyte proliferation and lymphokine production in response to various mitogens and fungal antigens, and the effect of cryptococcal capsular polysaccharide on all these activities is being determined. Yeast factors that potentiate infection or interfere with normal host cell functions are being characterized. It is anticipated that these findings will eventually lead to improved methods for rapid diagnosis and treatment of cryptococcosis.